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Chronic Hepatitis

Important Points

Definition – Liver disorders in which hepatic inflammation and necrosis continue for at least 6 months.

Classification by cause – These are:

  1. Chronic viral hepatitis – hepatitis B, C and D
  2. Autoimmune hepatitis:
  3. Drugs – (alpha methyldopa, isoniazid)Q
  4. Alcoholic liver disease
  5. Non alcoholic steato hepatitis
  6. Metabolic – Wilson’s disease, hemochromatosis
  7. Cryptogenic
    1. Type I (anti actin/lupoid)Q
    2. Type II (Anti LKM)Q
    3. Type III (Anti soluble liver antigen)Q

Chronic persistent hepatitis Q is classified by grade as minimal or mild chronic hepatitis and by stage as absent or mild fibrosis.


Chronic lobular hepatitis Q is classified as mild to moderate grade and by stage as absent or minimal fibrosis.


Chronic active hepatitis Q is classified as mild to severe grade and mild to severe fibrosis by staging.


Piecemeal necrosis Q is the minimal histological requirement to establish the diagnosis of chronic active hepatitis.


Extra Edge Chronic persistent hepatitis can be differentiated from chronic active hepatitis only by histopathology. (LQ 2012)

Chronic Viral Hepatitis
  1. Piecemeal Necrosis
  2. Portal fibrosis
  3. Bridging Necrosis
  4. Interface hepatitis
  5. Ground Glass Appearance
Hepatitis C – Macro Vesicular Steatosis
Hepatitis D – Micro Vesicular Steatosis
Hepatitis E – Marked Cholestasis


Important Points

Chronic Viral Hepatitis


Clinical and laboratory features suggest progression of acute hepatitis to chronic hepatitis: (Ref. Hari. 18th ed., Pg-1945)

  1. Lack of complete resolution of clinical symptoms of anorexia, weight loss, and fatigue and the persistence of hepatomegaly;
  2. The presence of bridging/interface or multilobular hepatic necrosis on liver biopsy during protracted, severe acute viral hepatitis;
  3. Failure of the serum aminotransferase, bilirubin, and globulin levels to return to normal within 6–12 months after the acute illness;
  4. The persistence of HBeAg for >3 months or HBsAg for >6 months after acute hepatitis.


Classification of hepatitis is based on
  1. Cause - Depends on causative organism
  2. Grade -
    1. Histological Activity index (0–6)
    2. METAVIR score (0 to 4)
  3. Stage - Depends on fibrosis
Chronic hepatitis B
  1. After acute hepatitis B, chances of chronicity depends on the age.
  2. Infection at birth is associated with a clinically silent acute infection but 90% chances of chronic infection.
  3. While the infection in young adulthood is associated with clinically apparent acute hepatitis with a risk of 1% of chronicity.
  4. The clinical features range from asymptomatic infection to fatal hepatic failure.
  5. Fatigue is the most common symptom, along with intermittent deepening of jaundice, malaise and anorexia.
Complications of hepatitis:
  1. Relapsing hepatitis (Biochemical + Clinical) – seen in hepatitis A
  2. Cholestatic hepatitis – seen in hepatitis E
  3. Serum sickness like syndrome – hepatitis BQ
  4. Essential mixed cryoglobulinemia – hepatitic CQ
  5. Fulminant hepatitis – mainly seen in hepatitis Q B, C, E (Pregnancy).
  6. Chronic hepatitis – Hepatitis B, C. Hepatitis D coinfection does not affect the chronicity of acute hepatitis B infection. Superinfection and hepatitis D increases the severity of chronic hepatitis B.
  7. Hepato cellular carcinoma – hepatitis B, C (B > C)
  8. Gianotti – Crosti syndrome – In children, hepatitis B presents with anicteric hepatitis, a non-pruritic papular rash Q of face, buttocks and limbs and lymphadenopathy. (Papular acrodermatitis of childhood) (Ref. Hari. 18th ed., pg-2553)
  9. Ascites
  10. Coagulopathy
  11. Hypersplenism
  12. Arthritis
  13. Purpuric cutaneous lesions (leuko cytoclastic vasculitis)Q
  14. Immune complex glomerulonephritis Q Membranous GN (Child), MPGN, mesangiocapillary (Adult)
  15. Polyarteritis nodosa. (Hepatitis B)
  16. Pancreatitis, myocarditis, atypical pneumonia, aplastic anemia, transverse myelitis, and peripheral neuropathy.

Extra Edge Gall stone is not a complication (Focal & Segmental Glomerulo sclerosis is not a complication)


No Antiviral drugs is given in acute viral hepatitis B (Ref. Hari. 18th ed., Page - 2554)
  1. In Acute Hepatitis B, recovery occurs in ~99%; therefore, antiviral therapy is not likely to improve the rate of recovery and is not required.
  2. Severe acute hepatitis B is not an indication for anti viral therapy. Only supportive treatment is given.
Chronic Hep B
  1. Although progression to cirrhosis is more likely in severe than in mild or moderate chronic hepatitis B, all forms of chronic hepatitis B can be progressive, and progression occurs primarily in patients with active HBV replication.
  2. In populations of patients with chronic hepatitis B who are at risk for HCC, the risk is highest for those with continued, high-level HBV replication.
  3. Therefore, management of chronic hepatitis B is directed at suppressing the level of virus replication.
Five drugs have been approved for treatment of chronic hepatitis B:
  1. Injectable interferon (INF)α;
  2. Pegylated interferon [long-acting IFN bound to polyethylene glycol (PEG), known as PEG IFN];
  3. Lamivudine
  4. Adefovir dipivoxil
  5. Entecavir.
Recent Advance: Newer Drugs (Ref. Hari. 18th ed., Pg - 2569)
  1. Emtricitabine
  2. Tenofovir
  3. Telbivudine
  4. Pradefovir
  5. Clevudine
Indication of antiviral drug in chronic hepatitis B
  1. No treatment is indicated for asymptomatic non replicative hepatitis B carriers (undetectable HbeAg with normal
  2. ALT and HBV DNA <104 copies/mL documented serially over time).
  3. Assessment of need for antiviral therapy in Chronic hepatis B
  4. Antiviral therapy is indicated for patients with active HBV replication.
  5. Active HBV replication is best assessed by measuring serum HBe Ag levels and HBV DNA levels.
Patients with chronic hepatitis B (HBsAg - Positive) (Ref. Hari. 18th ed., Pg - 2569)


Summary of treamtent:
Treat a case of chronic hepatitis B only If there is increase in DNA copies & raised ALT !!! (LQ 2012)


Chronic Hepatitis C
Chronic hepatitis C is M/C cause of chronic liver disease (Ref. Hari. 18th ed., pg-2579)
Clinical features:
  1. Fatigue is the most common symptomQ
  2. Jaundice is mild
  3. Immune complex mediated extrahepatic complications of chronic hepatitis C are less common than chronic hepatitis B, with the exception of essential mixed cryoglobulinemia.
  4. Other extrahepatic complications unrelated to immune complex are Sjögren’s syndrome, lichen planus, and porphyria cutanea tarda.Q
  5. Membranous GN and Type I membranoproliferative GN can occur.
Laboratory features:
Anti LKM 1 antibodies are Q seen (also seen in auto immune hepatitis type II).
Characteristic episodic pattern of aminotransferase activity is seen in hepatitis C.
Hepatitis C: HCV RNA detection is the most sensitive test for HCV infection. It is commonest to spread by blood transfusion.


Extra Edge
  1. It is M/C due to blood transfusion
  2. No Vaccine available
  3. High Malignant Potential is there
  4. Associated with porphyria cutanea tarda and mix essential mixed cryoglobulinemia
Persistence of antibodies of HCV for > 6 months + Positive HCV RNA in serum (Ref. Hari. 18th ed., Pg - 2579)
Patient has chronic hepatitis C
Elevated ALT Normal ALT
Treatment can be started without liver biopsy Perform liver biopsy to obtain histological diagnosis and stage of chronic hepatitis

Evidence of chronic hepatitis on histopathology (at least moderate grade) is an indication for starting treatment (even in patients with normal ALT)
Prophylaxis of hepatitis C
No active or passive immunization is available
Drugs: First line therapy- pegylated IFN alpha 2a. Once weekly + ribavirin.


Recent Advances: New Drug
Sofosbuvir can effectively cure hepatitis in 90 percent of patients: This is not given in Harrison 18th edition also. !!!)


Factors associated with reduced responsiveness.
  1. Geno type I
  2. High level HCV RNA (>2 million copies/ml or >8,00,000 IU/ml)
  3. Advanced fibrosis (bridging fibrosis, cirrhosis)
  4. Long duration disease
  5. Age >40 years
  6. High HCV quasispecies diversity
  7. Male gender
  8. Immuno suppression
  9. Reduced adherence
  10. Obesity
  11. Hepatic steatosis
Reye syndrome (Fatty liver with encephalopathy)
  1. It is a rare and severe complication of influenza (usually B type) and other viral diseases (eg, varicella), particularly in young children.
  2. It consists of rapidly progressive hepatic failure and encephalopathy, and there is a 30% fatality rate.
  3. The pathogenesis is unknown, but the syndrome is associated with aspirin use in a variety of viral infections.
  4. Hypoglycemia, elevation of serum aminotransferases and blood ammonia, prolonged prothrombin time, and change in mental status all occur within 2–3 weeks after onset of the viral infection.
  5. Histologically, the periphery of liver lobules shows striking fatty infiltration and glycogen depletion.
  6. Treatment is supportive and directed toward the management of cerebral edema.
Important Points

Familial cause of chronic Jaundice

  1. Wilson
  2. Hemochromatosis
  3. α1 ATD
  4. Familial intrahepatic cholestasis
  5. Benign recurrent intrahepatic cholestasis
  6. Alagille syndrome


Essential Mixed Cryoglobulinemia (Ref. Hari. 18th ed., Page - 2798)
  1. Cryoglobulins are cold-precipitable monoclonal or polyclonal immunoglobulins.
  2. Cryoglobulinemia associated with a systemic vasculitis characterized by palpable purpura, arthralgias, weakness, neuropathy, and glomerulonephritis.
  3. In association with multiple myeloma, lymphoproliferative disorders, connective tissue diseases, infection, and liver disease, idiopathic hepatitis C.
  4. Rheumatoid factor is almost always found.
  5. Hypocomplementemia
  6. An elevated ESR and anemia occur frequently.
  7. Evidence for hepatitis C infection must be sought in all patients by testing for hepatitis C antibodies and hepatitis C RNA.
Autoimmune hepatitis: (Ref. Hari. 18th ed., Pg - 2585)
  1. Autoimmune hepatitis is a chronic disorder characterized by continuing hepatocellular necrosis and inflammation, usually with fibrosis which tends to progress to cirrhosis and liver failure.
  2. Autoantibody association in autoimmune hepatitis
    1. Hypergammaglobulinemia is common in autoimmune hepatitis.
    2. new categories of autoimmune hepatitis.
  1. Clinical Features of autoimmune hepatitis;
    1. Recurrent episodes of jaundice.
    2. ii. Usually young female.
    3. Fatigue, anorexia, amenorrhea, acne are common.
    4. Arthritis, cutaneous vasculitis, erythema, nodosum, colitis, sicca syndrome, pericarditis, pleurisy, anemia and azotemia occur.
  2. Treatment: Corticosteroids, Azathioprine (Ref. Hari. 18th ed., pg - 2587)
Extra Edge
  1. Anti LKM 1 (Anti LKM 1A – Hep C, Anti LKM 1B – Autoimmune Hep type II)
  2. Anti LKM 2 is seen in drug induced hepatitis.Q
  3. Anti LKM 3 is seen in chronic hepatitis D.Q

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